Psoriasis
Conditions
Keywords
Psoriasis, Topical, etanercept, clobetasol propionate
Brief summary
The primary hypothesis of this trial is that the addition of short courses of clobetasol propionate foam to etanercept monotherapy in subjects with moderate to severe plaque psoriasis will yield greater efficacy compared with etanercept monotherapy, as measured by PASI 75 at Week 12.
Interventions
DRUG1=Etanercept
50 mg SC bi-weekly for 12 weeks followed by 50 mg SC weekly for 12 weeks.
DRUG2=Clobetasol propionate foam
0.05% clobetasol propionate foam applied topically twice daily during two up-to-2 week courses
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has had stable moderate to severe plaque psoriasis for at least 6 months * Subject has involved BSA ≥ 10% and PASI ≥ 10 at screening and at baseline. * Subject is a candidate for systemic therapy or phototherapy in the opinion of the investigator
Exclusion criteria
* Subject has active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit. * Subject has evidence of skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of etanercept and/orclobetasol propionate foam on psoriasis. * Subject diagnosed with medication-induced or medication exacerbated psoriasis * Subject has any active Common Toxicity Criteria (CTC) grade 2 or higher infection * Subject has a significant concurrent medical condition or laboratory abnormalities as defined in the study protocol. * Subject has used any of the following therapies within 14 days of the first dose: UVB therapy or topical psoriasis therapies other than Class I or II topical steroids. * Subject has used any of the following therapies within 28 days of the first dose: Class I or II topical steriods, UVA therapy (with or without psoralen), or systemic psoriasis therapies * Subject has used one or more biologic therapies (other than interleukin (IL)12/IL23 inhibitors) within 3 months of the first dose * Subject has used an IL-12/IL-23 inhibitor within 6 months of the first dose of etanercept * Subject has ever used efalizumab (Raptiva®).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PASI 75 at Week 12 | Week 12 | The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 75 responses at week 12. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 75% reduction in the PASI score from Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PASI 90 at Week 12 | Week 12 | The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 90 responses at week 12. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 90% reduction in the PASI score from Baseline. |
| Patient Satisfaction at Week 12 | Week 12 | Patient assessment of treatment satisfaction status at week 12. It is a measure of a participant's level of satisfaction with the medication's control of psoriasis, ranging from very satisfied to very dissatisfied. |
| sPGA (0,1) at Week 12 | Week 12 | The percentage of participants achieving sPGA 0 or 1 at week 12. Static physician global assessment of psoriasis (sPGA) is a physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA of psoriasis comprises a 6-point scale ranging from 0 (clear) to 5 with increasing severity. |
| PASI 75 at Week 24 | Week 24 | The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 75 responses at week 24. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 75% reduction in the PASI score from Baseline. |
| sPGA (0,1) at Week 24 | Week 24 | The percentage of participants achieving sPGA 0 or 1 at week 24. Static physician global assessment of psoriasis (sPGA) is a physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA of psoriasis comprises a 6-point scale ranging from 0 (clear) to 5 with increasing severity. |
| Percent PASI Improvement From Baseline at Week 12 | Week 12 | The percentage of the improvement in PASI score at week 12 from baseline. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. |
Participant flow
Recruitment details
Participants were enrolled from 15 September 2010 through 17 October 2011.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept Monotherapy Etanercept 50 mg SC twice weekly for 12 weeks and then 50 mg SC once weekly for 12 weeks (a total of 24 weeks). | 297 |
| Etanercept + Clobetasol Propionate Foam Etanercept 50 mg SC twice weekly for 12 weeks and then 50 mg SC once weekly for 12 weeks (a total of 24 weeks). In addition, subjects received topical clobetasol propionate foam twice daily during weeks 11, 12, 23, and 24 as needed until skin was clear of detectable psoriasis (except in proscribed areas). | 295 |
| Total | 592 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative decision | 1 | 2 |
| Overall Study | Adverse Event | 4 | 6 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Ineligibility determined | 5 | 4 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Lost to Follow-up | 12 | 10 |
| Overall Study | Noncompliance | 1 | 2 |
| Overall Study | Other unspecified | 1 | 2 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Withdrawal by Subject | 15 | 9 |
Baseline characteristics
| Characteristic | Total | Etanercept + Clobetasol Propionate Foam | Etanercept Monotherapy |
|---|---|---|---|
| Age, Continuous | 44.1 Years STANDARD_DEVIATION 13.9 | 43.7 Years STANDARD_DEVIATION 14.2 | 44.6 Years STANDARD_DEVIATION 13.7 |
| Age, Customized < 65 years | 546 Participants | 273 Participants | 273 Participants |
| Age, Customized >=65 years | 46 Participants | 22 Participants | 24 Participants |
| BMI Categorical ≤ 35 kg/m^2 | 443 Participants | 221 Participants | 222 Participants |
| BMI Categorical > 35 kg/m^2 | 149 Participants | 74 Participants | 75 Participants |
| Dermatology life quality index (DLQI) | 14.3 STANDARD_DEVIATION 7.1 | 14.1 STANDARD_DEVIATION 7.4 | 14.6 STANDARD_DEVIATION 6.9 |
| Duration of psoriasis | 17.53 Years STANDARD_DEVIATION 11.59 | 17.39 Years STANDARD_DEVIATION 11.89 | 17.68 Years STANDARD_DEVIATION 11.31 |
| Patient assessment of treatment satisfaction Dissatisfied | 87 Participants | 47 Participants | 40 Participants |
| Patient assessment of treatment satisfaction Neither satisfied nor dissatisfied | 209 Participants | 100 Participants | 109 Participants |
| Patient assessment of treatment satisfaction Satisfied | 23 Participants | 13 Participants | 10 Participants |
| Patient assessment of treatment satisfaction Unknown | 40 Participants | 21 Participants | 19 Participants |
| Patient assessment of treatment satisfaction Very dissatisfied | 213 Participants | 103 Participants | 110 Participants |
| Patient assessment of treatment satisfaction Very satisfied | 20 Participants | 11 Participants | 9 Participants |
| Patient global assessment of psoriasis 0 | 0 Participants | 0 Participants | 0 Participants |
| Patient global assessment of psoriasis 1 | 3 Participants | 3 Participants | 0 Participants |
| Patient global assessment of psoriasis 2 | 10 Participants | 6 Participants | 4 Participants |
| Patient global assessment of psoriasis 3 | 107 Participants | 58 Participants | 49 Participants |
| Patient global assessment of psoriasis 4 | 212 Participants | 95 Participants | 117 Participants |
| Patient global assessment of psoriasis 5 | 251 Participants | 127 Participants | 124 Participants |
| Patient global assessment of psoriasis Unkown | 9 Participants | 6 Participants | 3 Participants |
| Psoriasis area severity index (PASI) | 18.51 Scores on a scale STANDARD_DEVIATION 8.72 | 18.85 Scores on a scale STANDARD_DEVIATION 9.16 | 18.17 Scores on a scale STANDARD_DEVIATION 8.25 |
| Psoriasis Body Surface Area(BSA) | 25.01 % STANDARD_DEVIATION 17.44 | 25.93 % STANDARD_DEVIATION 17.65 | 24.09 % STANDARD_DEVIATION 17.22 |
| Psoriatic arthritis No | 440 Participants | 227 Participants | 213 Participants |
| Psoriatic arthritis Yes | 152 Participants | 68 Participants | 84 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 36 Participants | 19 Participants | 17 Participants |
| Race/Ethnicity, Customized Black or African American | 31 Participants | 18 Participants | 13 Participants |
| Race/Ethnicity, Customized Mixed Race | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific | 6 Participants | 6 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 21 Participants | 12 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 491 Participants | 237 Participants | 254 Participants |
| Sex: Female, Male Female | 201 Participants | 100 Participants | 101 Participants |
| Sex: Female, Male Male | 391 Participants | 195 Participants | 196 Participants |
| Static physician global assessment of psoriasis (sPGA) 0 | 0 Participants | 0 Participants | 0 Participants |
| Static physician global assessment of psoriasis (sPGA) 1 | 2 Participants | 1 Participants | 1 Participants |
| Static physician global assessment of psoriasis (sPGA) 2 | 82 Participants | 46 Participants | 36 Participants |
| Static physician global assessment of psoriasis (sPGA) 3 | 340 Participants | 164 Participants | 176 Participants |
| Static physician global assessment of psoriasis (sPGA) 4 | 148 Participants | 74 Participants | 74 Participants |
| Static physician global assessment of psoriasis (sPGA) 5 | 18 Participants | 8 Participants | 10 Participants |
| Static physician global assessment of psoriasis (sPGA) Unknown | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 81 / 301 | 69 / 288 |
| serious Total, serious adverse events | 6 / 301 | 7 / 288 |
Outcome results
Primary
PASI 75 at Week 12
The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 75 responses at week 12. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 75% reduction in the PASI score from Baseline.
Time frame: Week 12
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept Monotherapy | PASI 75 at Week 12 | 48.3 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | PASI 75 at Week 12 | 65.2 Percentage of participants |
p-value: <0.00195% CI: [1.46, 2.87]Cochran-Mantel-Haenszel
Secondary
PASI 75 at Week 24
The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 75 responses at week 24. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 75% reduction in the PASI score from Baseline.
Time frame: Week 24
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept Monotherapy | PASI 75 at Week 24 | 63.6 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | PASI 75 at Week 24 | 69.3 Percentage of participants |
p-value: 0.13595% CI: [0.92, 1.85]Cochran-Mantel-Haenszel
Secondary
PASI 90 at Week 12
The percentage of participants with the Psoriasis Area and Severity Indexs (PASI) 90 responses at week 12. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity. A response was considered a 90% reduction in the PASI score from Baseline.
Time frame: Week 12
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept Monotherapy | PASI 90 at Week 12 | 19.4 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | PASI 90 at Week 12 | 29.7 Percentage of participants |
p-value: 0.00995% CI: [1.21, 2.64]Cochran-Mantel-Haenszel
Secondary
Patient Satisfaction at Week 12
Patient assessment of treatment satisfaction status at week 12. It is a measure of a participant's level of satisfaction with the medication's control of psoriasis, ranging from very satisfied to very dissatisfied.
Time frame: Week 12
Population: PRO analysis set, including all subjects randomized and also complete the baseline and at least 1 of the post-baseline PRO assessment with last observation carried forward (LOCF) imputation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etanercept Monotherapy | Patient Satisfaction at Week 12 | Dissatisfied | 4.9 Percentage of participants |
| Etanercept Monotherapy | Patient Satisfaction at Week 12 | Satisfied | 38.1 Percentage of participants |
| Etanercept Monotherapy | Patient Satisfaction at Week 12 | Neither satisfied nor dissatisfied | 14.7 Percentage of participants |
| Etanercept Monotherapy | Patient Satisfaction at Week 12 | Very satisfied | 39.5 Percentage of participants |
| Etanercept Monotherapy | Patient Satisfaction at Week 12 | Very dissatisfied | 2.8 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | Patient Satisfaction at Week 12 | Very satisfied | 51.8 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | Patient Satisfaction at Week 12 | Very dissatisfied | 3.9 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | Patient Satisfaction at Week 12 | Dissatisfied | 4.3 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | Patient Satisfaction at Week 12 | Neither satisfied nor dissatisfied | 5.3 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | Patient Satisfaction at Week 12 | Satisfied | 34.8 Percentage of participants |
p-value: 0.006Cochran-Mantel-Haenszel
Secondary
Percent PASI Improvement From Baseline at Week 12
The percentage of the improvement in PASI score at week 12 from baseline. PASI is an assessment of psoriasis based on severity of erythema, infiltration, and desquamation as well as area of involvement. The PASI score ranges from 0 to 72. The higher score represents the worse symptom severity.
Time frame: Week 12
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept Monotherapy | Percent PASI Improvement From Baseline at Week 12 | 68.18 Percentage of Improvement in PASI score | Standard Deviation 29.31 |
| Etanercept + Clobetasol Propionate Foam | Percent PASI Improvement From Baseline at Week 12 | 76.46 Percentage of Improvement in PASI score | Standard Deviation 24.01 |
p-value: <0.001van Elteren test
Secondary
sPGA (0,1) at Week 12
The percentage of participants achieving sPGA 0 or 1 at week 12. Static physician global assessment of psoriasis (sPGA) is a physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA of psoriasis comprises a 6-point scale ranging from 0 (clear) to 5 with increasing severity.
Time frame: Week 12
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept Monotherapy | sPGA (0,1) at Week 12 | 47.3 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | sPGA (0,1) at Week 12 | 63.1 Percentage of participants |
p-value: <0.00195% CI: [1.4, 2.75]Cochran-Mantel-Haenszel
Secondary
sPGA (0,1) at Week 24
The percentage of participants achieving sPGA 0 or 1 at week 24. Static physician global assessment of psoriasis (sPGA) is a physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA of psoriasis comprises a 6-point scale ranging from 0 (clear) to 5 with increasing severity.
Time frame: Week 24
Population: Intention-to-Treat with last observation carried forward (LOCF) imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept Monotherapy | sPGA (0,1) at Week 24 | 54.8 Percentage of participants |
| Etanercept + Clobetasol Propionate Foam | sPGA (0,1) at Week 24 | 61.7 Percentage of participants |
p-value: 0.13595% CI: [0.96, 1.87]Cochran-Mantel-Haenszel